4-Methyl-3-nitro-pyridin-2-ol; 4-Methyl-3-nitro-2-pyridinol -Drug Synthesis Database

【结构式】

【分子编号】14616

【品名】4-Methyl-3-nitro-pyridin-2-ol; 4-Methyl-3-nitro-2-pyridinol

【CA登记号】21901-18-8

【分子式】C₆H₆N₂O₃

【分子量】154.12532

【元素组成】C 46.76% H 3.92% N 18.18% O 31.14%

与该中间体有关的原料药合成路线共 2 条

合成路线1 合成路线2

合成路线1

该中间体在本合成路线中的序号：(III)

The diazonium salt from 2-amino-4-methylpyridine (I) is converted to 2-hydroxy-4-methylpyridine (II), which is nitrated to give 2-hydroxy-4-methyl-3-nitropyridine (III). Conversion to 2-chloro-4-methyl-3-nitropyridine (IV) is effected with phosphorous oxychloride and phosphorous pentachloride. Reduction of (IV) with hydrogen/Raney Nickel provides 3-amino-2-chloro-4-methylpyridine (V), which is condensed with 2-chloronicotinoyl chloride to give 2-chloro-N-(2-chloro-4-methyl-3-pyridinyl)-3-pyridinecarboxamide (VI). Treatment with cyclopropylamine affords N-(2-chloro-4-methyl-3-pyridinyl)-2-(cyclopropylamino)-3-pyridinecarboxamide (VII), which is cyclized in the presence of sodium hydride to yield nevirapine.

参考文献中间体

合成目标

【1】 Hargrave, K.D.; Grozinger, K.G.; Proudfoot, J.R.; et al.; Novel non-nucleoside inhibitors of HIV-1 reverse transcriptase. 1. Tricyclic pyridobenzo- and dipyridodiazepinones. J Med Chem 1991, 34, 7, 2231-41.
【2】 Riska, P.S.; Johnstone, J.N.; Silverstein, H.H.; Hattox, S.E.; Norris, S.H.; St. George, R.; Grob, P.M.; Hargrave, K.D.; Nevirapine. Drugs Fut 1992, 17, 10, 887.
【3】 Hargrave, K.D.; Merluzzi, V.J.; Labadia, M.; et al.; Inhibition of HIV-1 replication by a non-nucleoside reverse transcriptase inhibitor. Science 1990, 250, 4986, 1411-3.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
	15224	2-chloronicotinoyl chloride	49609-84-9	C₆H₃Cl₂NO	详情	详情
(I)	14614	2-Amino-4-picoline; 4-Methyl-2-pyridinamine; 4-Methyl-2-pyridinylamine; 2-Amino-4-methylpyridine	695-34-1	C₆H₈N₂	详情	详情
(II)	14615	4-methyl-2-pyridinol		C₆H₇NO	详情	详情
(III)	14616	4-Methyl-3-nitro-pyridin-2-ol; 4-Methyl-3-nitro-2-pyridinol	21901-18-8	C₆H₆N₂O₃	详情	详情
(IV)	14617	2-chloro-4-methyl-3-nitropyridine	23056-39-5	C₆H₅ClN₂O₂	详情	详情
(V)	14618	2-chloro-4-methyl-3-pyridinamine; 2-chloro-4-methyl-3-pyridinylamine	133627-45-9	C₆H₇ClN₂	详情	详情
(VI)	14619	2-chloro-N-(2-chloro-4-methyl-3-pyridinyl)nicotinamide		C₁₂H₉Cl₂N₃O	详情	详情
(VII)	14620	N-(2-chloro-4-methyl-3-pyridinyl)-2-(cyclopropylamino)nicotinamide; N-(2-chloro-4-methyl-3-pyridinyl)-2-(cyclopropylamino)-3-pyridinecarboxamide	133627-47-1	C₁₅H₁₅ClN₄O	详情	详情

合成路线2

该中间体在本合成路线中的序号：(I)

The cyclization of 4-methylpyridine-2-amine (I) with 2-bromoacetaldehyde (II) in refluxing ethanol gives 7-methylimidazo[1,2-a]pyridine (III), which by reaction with formaldehyde in refluxing acetic acid is converted into 7-methylimidazo[1,2-a]pyridin-3-ylmethanol (IV). Finally, this compound is condensed with 2-phenylethanethiol (V) in acetic acid at 100 C.

参考文献中间体

合成目标

【1】 Gueiffier, A.; Mavel, S.; Lhassani, M.; Elhakmaoui, A.; Snoeck, R.; Andrei, G.; Chavignon, O.; Teulade, J.C.; Witvrouw, M.; Balzarini, J.; De Clercq, E.; Chapat, J.P.; Synthesis of imidazo[1,2-a]pyridines as antiviral agents. J Med Chem 1998, 41, 25, 5108.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(I)	14616	4-Methyl-3-nitro-pyridin-2-ol; 4-Methyl-3-nitro-2-pyridinol	21901-18-8	C₆H₆N₂O₃	详情	详情
(II)	24802	2-bromoacetaldehyde		C₂H₃BrO	详情	详情
(III)	24803	7-methylimidazo[1,2-a]pyridine		C₈H₈N₂	详情	详情
(IV)	24804	(7-methylimidazo[1,2-a]pyridin-3-yl)methanol		C₉H₁₀N₂O	详情	详情
(V)	24805	2-phenyl-1-ethanethiol		C₈H₁₀S	详情	详情

Extended Information